The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.Read moreRead less
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less
Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed t ....Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed to establish the properties of the electric fields around cells and cell membrane interactions with these fields that enable molecular translocation. This fundamental science could have broad implications in the domains of drug delivery, gene therapy and neural stimulation.Read moreRead less
The combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.
Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology re ....Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology research in Australia. The project anticipates contributing to new tools for delivering genes to cells, benefiting therapeutic and biotechnology applications.Read moreRead less
Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cel ....Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cellular processes. The outcomes will include fundamental new knowledge in cell biology and lead to the development of unique biological models that can be used to understand disease.Read moreRead less
Synergistic nanostimulation of nerve cells using atomic force microscopy technology. The research will develop multifunctional nanoelectrodes for neural prosthetic devices of the future. They will be smaller and more effective, enabling integration with single neural networks in the body, to improve the clinical treatment of severe neurological disorders and loss of sensory (hearing and vision) and motor functions.